Antibody-drug Conjugate Information
General Information of This Antibody-drug Conjugate (ADC)
| ADC ID |
DRG0KQMWX
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| ADC Name |
hmAb-H541L11-DXd
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| Synonyms |
hmAb-H541L11-DXd
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| Organization |
DAIICHI SAMKO COMPANY, LIMITED
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| Drug Status |
Investigative
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| Drug-to-Antibody Ratio |
7.8
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| Structure |
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| Antibody Name |
hmAb-H541
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Antibody Info | ||||
| Antigen Name |
Leukocyte antigen CD37 (CD37)
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Antigen Info | ||||
| Payload Name |
Undisclosed
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| Therapeutic Target |
Stimulator of interferon genes protein (STING1)
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Target Info | ||||
| Linker Name |
Succinimidyl-4- (N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC)
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Linker Info | ||||
| Conjugate Type |
Random conjugation through reduced inter-chain cysteines.
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| Combination Type |
N-[6- (2,5-dioxo-2,5-dihydro-1h-pyrrol-1-yl) hexanoyl]glycylglycyl-phenylalanyl-n-[ (2-{[ (1s,9s)-9-ethyl-5-fluoro-9-hydroxy-4-methyl-10,13-dioxo-2,3,9,10,13,15-hexahydro-1h,12h-benzo[de]pyrano[3',4':6,7]indolizino[1,2-b]quinolin-1-yl]amino}-2-oxoethoxy)methyl]glycinamide
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ADC-specific functional property(2027 Update)
Circulating Stability
| Incubation Time | 5hr | Release | 98.6% | Reference |
[1]
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| Incubation Medium | Each anti-CD37 humanized antibody-diug conjugate dissolved at 20 mg/mL in ABS was diluted into 2 mg/mL with Otsuka physiological saline and left standing atroom temperature or 4°C. for 5 hours, the recovery rate of the anti-CD37 humanized antibody-drug conjugate was calculated. | ||||
| Description |
Evaluation of Recovery Rate of Anti-CD37 Humanized Antibody-Drug Conjugate into Physiological Saline.
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Binding Affinity
| Dissocation Constant (Kd) | Binding Target | Description | Reference |
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| 2000-2500 . |
CD37
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The binding activity was evaluated by flow cytometry on CD37-positive human diffuse large B-cell lymphoma cell line OCI-LY7 (DSMZ), the cells were suspended by the addition of each of the four antibody-drug conjugates or anegative control antibody-drug conjugate (hmAb-IgG1-DXd) produced using human IgG at each concentration, the MFI of antibody-drug conjugates at 100 ug/mL was measured.
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[1]
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General Information of The Activity Data Related to This ADC
Discovered Using Cell Line-derived Xenograft Model
Revealed Based on the Cell Line Data
Full List of Activity Data of This Antibody-drug Conjugate
Discovered Using Cell Line-derived Xenograft Model
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth lnhibition value (TGl) | < 30% | Positive CD37 expression (CD37+++/++) | ||
| Method Description |
CD37-positive human diffuse large B-cell lymphoma cell line SU-DHL-8 (ATCC) was subcutaneously inoculated at a dose of 5x106 cells to the right flank region of each five or six-week-old female SCID mouse (Day 0). On Day 7, the mice were randomly grouped. On the day of grouping, the antibodydrug conjugates hmAb-H11L11-DXd was intravenously administered at a dose of 1 mg/kg to the tail of each mouse. An antibody-drug conjugate (hmAb-IgG1-DXd) produced using human IgG was administered as a negative control at a dose of 3 mg/kg in the same manner as above. The long diameter and short diameter of the inoculated tumor were measured twice a week using electronic digital calipers, and the volume of the tumor was then calculated.
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| In Vivo Model | SU-DHL-8 (ATCC) female SCID mouse model | ||||
| Experiment 2 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth lnhibition value (TGl) | > 50% | Positive CD37 expression (CD37+++/++) | ||
| Method Description |
CD37-positive human diffuse large B-cell lymphoma cell line OCI-LY7 (DSMZ) was subcutaneously inoculated at a dose of 1x107 cells to the right flank region of each five or six-week-old female SCID mouse (Day 0). On Day 9, the mice were randomly grouped. On the day of grouping, the antibodydrug conjugates hmAb-H11L11-DXd was intravenously administered at a dose of 1 mg/kg to the tail of each mouse. An antibody-drug conjugate (hmAb-IgG1-DXd) produced using human IgG was administered as a negative control at a dose of 3 mg/kg in the same manner as above. The long diameter and short diameter of the inoculated tumor were measured twice a week using electronic digital calipers, and the volume of the tumor was then calculated.
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| In Vivo Model | OCI-LY7 (DSMZ) female SCID mouse model | ||||
| Experiment 3 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth lnhibition value (TGl) | > 50% | Positive CD37 expression (CD37+++/++) | ||
| Method Description |
CD37-positive human diffuse large B-cell lymphoma cell line WSU-DLCL2 (DSMZ) was subcutaneously inoculated at a dose of 1x107 cells to the right flank region of each five or six-week-old female SCID mouse (Day 0). On Day 11, the mice were randomly grouped. On the day of grouping, the antibodydrug conjugates hmAb-H11L11-DXd was intravenously administered at a dose of 1 mg/kg to the tail of each mouse. An antibody-drug conjugate (hmAb-IgG1-DXd) produced using human IgG was administered as a negative control at a dose of 3 mg/kg in the same manner as above. The long diameter and short diameter of the inoculated tumor were measured twice a week using electronic digital calipers, and the volume of the tumor was then calculated.
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| In Vivo Model | WSU-DLCL2 (DSMZ) female SCID mouse model | ||||
| Experiment 4 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth lnhibition value (TGl) | > 90% | Positive CD37 expression (CD37+++/++) | ||
| Method Description |
CD37-positive human diffuse large B-cell lymphoma cell line WSU-DLCL2 (DSMZ) was subcutaneously inoculated at a dose of 1x107 cells to the right flank region of each five or six-week-old female SCID mouse (Day 0). On Day 11, the mice were randomly grouped. On the day of grouping, the antibodydrug conjugates hmAb-H11L11-DXd was intravenously administered at a dose of 1 mg/kg to the tail of each mouse. An antibody-drug conjugate (hmAb-IgG1-DXd) produced using human IgG was administered as a negative control at a dose of 3 mg/kg in the same manner as above. The long diameter and short diameter of the inoculated tumor were measured twice a week using electronic digital calipers, and the volume of the tumor was then calculated.
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| In Vivo Model | WSU-DLCL2 (DSMZ) female SCID mouse model | ||||
| Experiment 5 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth lnhibition value (TGl) | > 99% | Positive CD37 expression (CD37+++/++) | ||
| Method Description |
CD37- positive human chronic lymphocytic leukemia cell line JVM-3 (DSMZ) was subcutaneously inoculated at a dose of 3x106 cells to the right flank region of each female SCID mouse (Day 0). On Day 13, the mice were randomly grouped. On the day of grouping, hmAb-H541L11-DXd was intravenously administered to the tail of each mouse at 1 mg/kg.
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| In Vivo Model | JVM-3 (DSMZ) female SCID mouse model | ||||
| Experiment 6 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth lnhibition value (TGl) | > 100% | Positive CD37 expression (CD37+++/++) | ||
| Method Description |
CD37-positive human diffuse large B-cell lymphoma cell line OCI-LY7 (DSMZ) was subcutaneously inoculated at a dose of 1x107 cells to the right flank region of each five or six-week-old female SCID mouse (Day 0). On Day 9, the mice were randomly grouped. On the day of grouping, the antibodydrug conjugates hmAb-H11L11-DXd was intravenously administered at a dose of 1 mg/kg to the tail of each mouse. An antibody-drug conjugate (hmAb-IgG1-DXd) produced using human IgG was administered as a negative control at a dose of 3 mg/kg in the same manner as above. The long diameter and short diameter of the inoculated tumor were measured twice a week using electronic digital calipers, and the volume of the tumor was then calculated.
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| In Vivo Model | OCI-LY7 (DSMZ) female SCID mouse model | ||||
| Experiment 7 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth lnhibition value (TGl) | > 100% | Positive CD37 expression (CD37+++/++) | ||
| Method Description |
CD37-positive human diffuse large B-cell lymphoma cell line SU-DHL-8 (ATCC) was subcutaneously inoculated at a dose of 5x106 cells to the right flank region of each five or six-week-old female SCID mouse (Day 0). On Day 7, the mice were randomly grouped. On the day of grouping, the antibodydrug conjugates hmAb-H11L11-DXd was intravenously administered at a dose of 1 mg/kg to the tail of each mouse. An antibody-drug conjugate (hmAb-IgG1-DXd) produced using human IgG was administered as a negative control at a dose of 3 mg/kg in the same manner as above. The long diameter and short diameter of the inoculated tumor were measured twice a week using electronic digital calipers, and the volume of the tumor was then calculated.
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| In Vivo Model | SU-DHL-8 (ATCC) female SCID mouse model | ||||
| Experiment 8 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth lnhibition value (TGl) | > 100% | Positive CD37 expression (CD37+++/++) | ||
| Method Description |
CD37- positive human chronic lymphocytic leukemia cell line JVM-3 (DSMZ) was subcutaneously inoculated at a dose of 3x106 cells to the right flank region of each female SCID mouse (Day 0). On Day 13, the mice were randomly grouped. On the day of grouping, hmAb-H541L11-DXd was intravenously administered to the tail of each mouse at 3 mg/kg.
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| In Vivo Model | JVM-3 (DSMZ) female SCID mouse model | ||||
| Experiment 9 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth lnhibition value (TGl) | > 100% | Positive CD37 expression (CD37+++/++) | ||
| Method Description |
CD37- positive human follicular lymphoma cell line DOHH-2 (DSMZ) was subcutaneously inoculated at a dose of 1x106 cells to the right flank region of each female SCID mouse (Day 0). On Day 21, the mice were randomly grouped. On the day of grouping, hmAb-H541L11-DXd was intravenously administered to the tail of each mouse at 1 mg/kg.
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| In Vivo Model | DOHH-2 (DSMZ) female SCID mouse model | ||||
| Experiment 10 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Tumor Growth lnhibition value (TGl) | > 100% | Positive CD37 expression (CD37+++/++) | ||
| Method Description |
CD37- positive human follicular lymphoma cell line DOHH-2 (DSMZ) was subcutaneously inoculated at a dose of 1x106 cells to the right flank region of each female SCID mouse (Day 0). On Day 21, the mice were randomly grouped. On the day of grouping, hmAb-H541L11-DXd was intravenously administered to the tail of each mouse at 3 mg/kg.
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| In Vivo Model | DOHH-2 (DSMZ) female SCID mouse model | ||||
Revealed Based on the Cell Line Data
| Experiment 1 Reporting the Activity Date of This ADC | [1] | ||||
| Efficacy Data | Half Maximal inhibitory Concentration (lC50) | ≈ 0.7 nM | Positive CD37 expression (CD37+++/++) | ||
| Method Description |
human diffuse large B-cell lymphoma cell line OCI-LY7 (DSMZ) , 5x10-cells/100 ML/well , IMDM medium , hmAbH541L11-DXd was added to the cells such that the final concentrations were from 0.0064 nM to 20 nM. The cells were cultured under conditions of 37°C. and 5% CO2 for 6 days, and thereafter, the number of live cells was measured.
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| In Vitro Model | Diffuse large B-cell lymphoma germinal center B-cell type, Diffuse large B-cell lymphoma | OCI-LY7 cells | CVCL_1881 | ||